Pharm- Cardiovascular System

Front 1

What is the neurotransmitter at found at all autonomic ganglia?

Back 1

Acetylcholine

Front 2

Where is the origin of the postganglionic sympathetic nerves found?

Back 2

Paravertebrally near the CNS, along side the thoracolumbar region of the spine

Front 3

Where is the origin of the postganglionic parasympathetic nerves found?

Back 3

In the craniosacral regions close to their target organs

Front 4

Which branch of the ANS does a cholinomimetic agent work on?

Back 4

The parasympathetic branch and it works to stimulate through muscarinic receptors.

Front 5

Which branch of the ANS does a cholinolytic agent work on?

Back 5

The parasympathetic branch and it works to inhibit through blocking the action of muscarinic receptors.

Front 6

What are the three roles of acetylcholine in the nervous system?

Back 6

1) NT at all autonomic ganglia
2) NT of the parasympathetic effector sites where it acts on muscarinic receptors
3) At the neuro-myelo junction at muscles

Front 7

Explaion where are the main baroreceptors for blood pressure located and how can they become dysfunctional?

Back 7

They are located in the carotid sinus and the aortic arch. They can become dysfunctional through atherosclerosis and calcification, by hardening and not being able to stretch and sense pressure change like they normally would

Front 8

What two jobs can the vagus (X) nerve do in the heart?

Back 8

Slow the firing of the SA node (heart rate) and slow the conduction from the SA to the AV (communication)

Front 9

Does the parasympathetic system have more control over the ventricles or the atria?

Back 9

The atria and the rest of the region. There is very little parasympathetic innervation below the AV groove.

Front 10

Which system has a larger ratio of preganglionic to post ganglionic fibers: parasympathetic or sympathetic?

Back 10

Parasympathetic 1:1! vs 1:20 for sympathetic

Front 11

Compare the NTs and receptors found at target tissues in the sympathetic and parasympathetic systems.

Back 11

The sympathetic system uses Norepinephrine and Adrenergic receptors (alpha and Beta); the parasympathetic system uses Acetylcholine and Cholinergic Muscarinic receptors

Front 12

Compare the NTs and receptors found in the autonomic ganglia of the sympathetic and parasympathetic systems.

Back 12

Both systems use Acetylcholine and Cholinergic Nicotinic receptors

Front 13

What is the exception to the rule that the sympathetic nervous system uses NE and Adrenergic receptors in its target tissues?

Back 13

The Sweat Glands where the sympathetic nervous system uses Acetylcholine and Cholinergic Muscarinic receptors

Front 14

What NT/receptor combo is used by the sympathetic nervous system to target the the Renal vascular smooth muscle?

Back 14

Dopamine and the Dopaminergic receptor

Front 15

Which NTs does the sympathetic nervous system use when sending messages from the adrenal medulla?

Back 15

Epinephrine and Norepinephrine

Front 16

What NT/receptor combo does the somatic nervous system use at its target tissues?

Back 16

Acetylcholine and Nicotinic receptors

Front 17

What is the main source of fuel for the heart?

Back 17

Free fatty acids; this is why the sympathetic nervous system has a lipolytic effect during the fight or flight response

Front 18

Where in the body do we find muscarinic receptors?

Back 18

In the target tissues of the parasympathetic system, and in sweat glands as targets of the sympathetic system

Front 19

Where in the body do we find nicotinic receptors?

Back 19

In all autonomic ganglia, and in the neuro-muscular junction of the somatic nervous system

Front 20

Where is acetylcholinesterase and butyrlcholinesterase found in the body?

Back 20

Acetylcholinesterase is ubiquitous at synaptic junctions and butyrlcholinesterase is found in the blood.

Front 21

What is Pilocarpine used for?

Back 21

Glaucoma

Front 22

What is the ion that controls the stimulation of the SA and AV nodes?

Back 22

Ca++

Front 23

How does parasympathetic stimulation affect the resting potential of the SA and AV nodes?

Back 23

It makes it more negative and less likely to reach threshold, thereby slowing down firing and conduction rates

Front 24

What effects do the muscarinic receptors of the heart have on SA function and AV function?

Back 24

They slow rate of firing of the SA node and decrease the conduction of the AV node

Front 25

What effects do the B1 adrenergic receptors in the heart have on SA and AV function?

Back 25

They increase the rate of firing of the SA node and increase the conduction of the AV node, as well as increase the overall contractility of the heart

Front 26

What is the second messenger system of the B1 receptor in the myocyte?

Back 26

cAMP

Front 27

Sympathetic tone will constrict most blood vessels through activation of which receptor?

Back 27

Alpha 1

Front 28

Sympathetic tone will cause vasodilation in most BVs found in what type of body tissue, due to which receptor?

Back 28

Skeletal muscle; Beta 2

Front 29

What type of receptors are curiously found in all vascular beds and why is it curious?

Back 29

Muscarinic receptors; this is curious because muscarinic receptors are mainly use by the parasympathetic nervous system, but there is not much parasympathetic innervation that occurs in the vascular beds

Front 30

BV tone is mainly regulated by which receptor of the sympathetic nervous system?

Back 30

Alpha 1

Front 31

During the fight or flight response what is responsible for sustained vasodilation in skeletal muscle long after the initial effects of the sympathetic response?

Back 31

Adenosine from the breakdown of ATP

Front 32

Which sympathetic receptors are present in bronchial glands and what do they do?

Back 32

Alpha 1 receptors; decrease secretion

Front 33

Which parasympathetic receptors are present in bronchial glands and what do they do?

Back 33

Muscarinic receptors; increase secretion

Front 34

Which sympathetic receptors are present in bronchial smooth muscle and what do they do?

Back 34

Beta 2; bronchodilate

Front 35

Which parasympathetic receptors are present in bronchial smooth muscle and what do they do?

Back 35

Muscarinic; bronchoconstrict

Front 36

Which sympathetic receptors are present in GI smooth muscle and what do they do?

Back 36

Alpha 2 (also Beta receptors); decrease motility

Front 37

Which sympathetic receptors are present in sphincter smooth muscle and what do they do?

Back 37

Alpha 1(also Beta); contraction

Front 38

Which sympathetic receptors influence gastric secretion and what do they do?

Back 38

Alpha 2 (also Beta); inhibit secretions

Front 39

Which sympathetic receptors are present in bladder wall (Detrusser) smooth muscle and what do they do?

Back 39

Beta 2; relax the smooth muscle

Front 40

Which sympathetic receptors are present in bladder sphincter (Trigone) smooth muscle and what do they do?

Back 40

Alpha 1; contract

Front 41

Where is the exception to the rule that parasympathetic nerves do not innervate vascular beds?

Back 41

The corpra and small blood vessels of the penis

Front 42

What disorder are viagra-like drugs used to treat in some women between the 3rd-4th decade of life?

Back 42

Pulmonary Hypertension

Front 43

In erection what does Point and Shoot mean?

Back 43

Parasympathetic/Sympathetic

Front 44

Which sympathetic receptors are present in salivary glands and what do they do?

Back 44

Alpha 1; produce viscous secretions

Front 45

Which sympathetic receptors are present in lacrimal glands and what do they do?

Back 45

Alpha: secretion

Front 46

Which parasympathetic receptors are present in lacrimal glands and what do they do?

Back 46

Muscarinic; copious secretions

Front 47

When it comes to Eccrine (generalized) sweating what is the receptor used by the sympathetic nervous system and what is causing the sympathetic stimulation?

Back 47

Muscarinic; Thermoregulation

Front 48

When it comes to Apocrine (localized) sweating (e.g. head and palms) what is the receptor used by the sympathetic nervous system and what is causing the sympathetic stimulation?

Back 48

Alpha receptors; mental/psychological stress

Front 49

Contraction of which muscle is responsible for pupil constriction and what are the receptors that cause this contraction? Which branch of the autonomic nervous system does this.

Back 49

The Circular Muscle of the iris and Muscarinic receptors are responsible for this response; Parasympathetic branch

Front 50

Contraction of which muscle is responsible for pupil dilation and what are the receptors that cause this contraction? Which branch of the nervous system does this?

Back 50

The Radial Muscle of the iris and Alpha 1 receptors are responsible for this; Sympathetic branch

Front 51

Which muscle of the eye is responsible for movement of fluid out of the globe and lens accommodation for near vision? Which receptors and branch of the nervous system are responsible for this?

Back 51

The Ciliary muscles, muscarinic receptors and the parasympathetic nervous system

Front 52

What ion is responsible for NT release from presynaptic terminals?

Back 52

Ca++

Front 53

At low therapeuptic doses which branches of the circulatory system does Nitroglycerine preferentially dilate?

Back 53

Preferentially dilates the veins because there is more NO release and production that occurs in response to Nitro in the veins than in the arteries

Front 54

What medication is commonly give with Nitroglycerin and why?

Back 54

Beta blockers; Nitroglycerine will cause the veins to dilate and contribute a decrease in blood pressure. This is turn will cause an increased sympathetic response as the heart tries to maintain BP constant by increasing heart rate (undesired effect). Beta blockers are given to stop this unwanted increase in HR

Front 55

What effect does intravenous acetylcholine have on blood pressure and why?

Back 55

It decreases BP because it is a vasodilator and acts on muscarinic receptors on the endothelial cells of vascular beds to produce NO.

Front 56

What purpose do the muscarinic receptors on the endothelial cells of vascular beds serve and are they activated endogenously or pharmacologically?

Back 56

Their purpose is unknown since there seems to be no parasympathetic innervation to them. Thus, their main method of activation is pharmacological because the parasympathetic system seems to have little affect.

Front 57

What two hemodynamic components are related to BP?

Back 57

Peripheral resistance and Cardiac output

Front 58

Increases in peripheral resistance in the cardiovascular system are mediated by which sympathetic receptors?

Back 58

Alpha 1 and Alpha 2

Front 59

Pulse pressure is related to cardiac output, which is related to contractility of the myocardium, which is controlled by what sympathetic receptor?

Back 59

Beta 1

Front 60

What is the major mechanism of attenuated response after stimulation of a postsynaptic terminal with a NT?

Back 60

Reuptake > Diffusion > Degredation

Front 61

Which receptors is low dose epinephrine more selective for Alpha or Beta, and which subtype? What does this mean for vasculature the effect on BP?

Back 61

Beta 2 receptors. This will cause vasodilation and a decrease in BP

Front 62

Where does epinephrine get released from?

Back 62

The adrenal medulla

Front 63

Why do you get a fall in BP at the end of a High Dose Epinephrine response?

Back 63

Because it starts to act like Low Dose Epinephrine

Front 64

Which adrenergic receptors dose epinephrine activate?

Back 64

All the adrenergic receptors: all the Alphas and all the Betas, including Beta 3

Front 65

What effect does a blocking dose of atropine have on BP?

Back 65

It has no effect because atropine blocks the effects of the parasympathetic system, but it is the sympathetic nervous system that is responsible for the changes in peripheral resistance and cardiac output that affect BP

Front 66

What receptors does Isoproterenol work on most?

Back 66

Beta 2; produces dramatic drops in BP
Beta 1; increases the contractility of myocardium

Front 67

Does Isoproterenol look like High Dose Epinephrine?

Back 67

No, it is just the opposite

Front 68

Compare the receptor profiles for Isoproterenol and Epnephrine.

Back 68

Isoproterenol affects the same receptors as epinephrine except it does not do the Alpha 1s and Alpha 2s

Front 69

Explain what mechanism does the chemical Tyramine uses to elicit it very prolonged response?

Back 69

Tyramine must get into the nerve terminals and gets taken up by reuptake mechanisms and kicks out norepinephrine. This gives a prolonged pressor response

Front 70

What medication uses a mechanism of action similar to the chemical Tyramine?

Back 70

Ephedrine; but ephedrine also directly stimulates at nerve terminals in addition to having similar indirect effects that Tyramine does

Front 71

When do you see hypertension and tachycardia at the same time in a person?

Back 71

When they are taking Cocaine or amphetamines. Cocaine stimulates sympathetic outflow and has an effect on blocking reuptake of catecholamines

Front 72

Will Tyramine's effect on BP be changed after pre-treatment with cocaine?

Back 72

Yes- it will not have it's same effect because it cannot get into the nerve terminal through its reuptake mechanism

Front 73

What experimental question can Tyramine be used to answer?

Back 73

Is there a block in reuptake.

Front 74

What type of receptors does Phentolamine block? Is it competitive or non-competitive?

Back 74

Alpha 1 and Alpha 2; competitive

Front 75

Which receptors help provide negative feedback for the release of Norepinephrine? What Alpha blocker stops this appropriate negative feedback and can cause reflex tachycardia?

Back 75

Pre-synaptic Alpha 2 receptors (in the NTS in particular); Phentolamine because it blocks both Alpha 1 and Alpha 2

Front 76

What drugs can cause Epinephrine reversal and why?

Back 76

Alpha blockers, because you have the unopposed vasodilatory and ionotropic responses of Beta 2 and Beta 1 receptors respectively, now that the Alpha receptors in the vascular periphery are blocked

Front 77

Which receptors does propranolol block? Why would it give you a drop in blood pressure?

Back 77

Beta 1 and Beta 2 receptors; non-selective beta blocker; Beta 1 controls the increased ionotropic effect seen in heart muscle

Front 78

What are the two type of Cholinesterase inhibitors?

Back 78

Carbamates (reversible inhibitor) and Organophosphates (irreversible inhibitor)

Front 79

What is Physostigmine used to treat and what special boundary does it cross?

Back 79

It is used to treat cholinergic syndrome and it is able to cross the BBB

Front 80

What is Neostigimine used to treat and what special barrier can't it cross?

Back 80

It is used to treat Mysthinia Gravis and it cannot cross the BBB

Front 81

What drug is only short acting and used to treat MG?

Back 81

Edrophonium

Front 82

Which organophosphate is used to treat glaucoma as an anticholinesterase?

Back 82

Echothiophate

Front 83

List the organophosphate anticholinesterase war gases in order of faset to slowest enzyme-binding potential.

Back 83

Soman > Sarin > VX

Front 84

What does the mneumonic SLUDE or DUMBELSS describe what are they refering to?

Back 84

They describe the effects of Anticholinesterase poisoning:

Diarrhea
Urination
Miosis/Muscle weakening
Bronchoconstriction
Bradycardia
Emesis
Lacrimation
Salivation
Sweating

Front 85

In anticholinesterase poisoning, symptoms due to which receptors are the most deadly and why?

Back 85

The Muscarinic symptoms; they are the most deadly because of respiratory compromise due to bronchoconstriction, bronchial secretions and CNS-respiratory failure

Front 86

What is the Rx for AChEI poisoning with a Carbamate and how does it work?

Back 86

Atropine, which also has a wide therapeutic index (compared with that of 2-PAM for Organophosphates), is an antimuscaric agent, so it blocks the receptors

Front 87

What is the Rx for AChEI poisoning with Organophosphates and how does it work?

Back 87

2-PAM (Pralidoxime), which has a very narrow therapeutic index (because it has NMJ blocking side effects), but which actually prevents the irreversible binding of organophosphates with AChE (but must be given BEFORE AGING occurs)

Front 88

Name the drugs that are anti muscarinic.

Back 88

Atropine, Scopalamine, Ipratropium Bromide, Glycopyrrolate

Front 89

Which Muscarinic receptors does Atropine work on and what function does it serve in eye exams?

Back 89

m1-m5; it functions to dilate the pupil by inhibiting parasympathetic tone of the ciliary muscle (Mydirasis and cycloplegia)

Front 90

What are the natural sources that contain Atropine and Scopalamine?

Back 90

Atropa belladonna (deadly nightshade) and Jimson Weed

Front 91

When is atropine contraindicated?

Back 91

Narrow angle glaucoma

Front 92

Why are atropines sometimes used before surgery?

Back 92

Because the salivary glands and other secretory sites are particularly sensitive to muscarinic blockade and they can prevent secretory complications with airways

Front 93

Compare the CNS effects of Atropine and Scopalamine and why?

Back 93

Scopalamine has greater CNS effects because it can cross the BBB and Atropine cannot

Front 94

What are the therapeutic uses of Scopalamine?

Back 94

Given prophylactically for motion sickness, and for treatment of side effects of Parkinson's Rx's and some antipsychotics

Front 95

What condition are antimuscarinics use for with regard to heart rate?

Back 95

Bradycardia; reduces vagal tone and brings heart rate up to a physiological range and keeps more stable

Front 96

What are some of the effects of anticholinergics on the respiratory system?

Back 96

Decreased secretion of bronchal mucus, reversal of any vagal-mediated bronchoconstriction

Front 97

What anticholinergic is given to treat asthma? Why are there no CNS effects?

Back 97

Ipratropium; it quaternary and gets stuck in the lung, so it cannot get to the brain

Front 98

What are the 5 cardinal signs of Anticholinergic toxicity?

Back 98

1) Blind as a Bat
2) Dry as a Bone
3) Red as a Beet
4) Hot as Hell
5) Mad as a Hatter

Front 99

Provide a summary of the Therapeutic indications for Antimuscarinics.

Back 99

-Presurgical adjunct to decrease bronchal secretions
-Eye exams
-ICU Tx of sinus bradycardia and AVN block
-Prevent motion sickness
-Asthma
-Parkinsonism
-Antidote to Anticholinesterase

Front 100

Tubocurarine is the prototypic non-depolarizing NMJ blocking agent. What are the three mechanisms by which it works?

Back 100

Competitive inhibition at low doses, higher doses can also inhibit ACh release from presynaptic terminals, and very high doses can also block the nicotinic channel

Front 101

Tubocurarine is often given pre-surgically to facilitate intubation and help immobilize the patient. How do you reverse these effects after surgery is over?

Back 101

NMJ blockade can be over come with ACh and an AChEI (e.g. neostigmine). Atropine or Glycopyrrolate are also given to prevent muscarinic effects of neostigmine.

Front 102

Is Tubocurarine specific or selective for NMJs?

Back 102

Selective! NOT specific..

Front 103

What is the main depolarizing NMJ blockin agent? Is it an agonist or antagonist?

Back 103

SuccinylCoA; it is an agonist with rapid onset and rapid hydrolysis (short action).

Front 104

Describe the three phases of SuccinylCoA action.

Back 104

Initially- there is depolarization of the muscle end plate and fasciculations can be seen on the skin

PHASE I- continuous depolarization prevents the generation of additional muscle contractions and leads to flaccid paralysis

PHASE II- with continuous administration the end plate hyperpolarizes, but is desensitized to the effects of ACh

Front 105

What are some of the more prominent adverse side effects seen wtih SuccinylCoA administration?

Back 105

Hyperkalemia, muscle pain, malignant hyperthermia (occurs with a genetic mutation)

Front 106

How does Botulinum toxin work?

Back 106

It degrades SNARE vesicle docking proteins in presynaptic terminals and prevents vesicular release of ACh

Front 107

What are some therapeutic indications for Botox that are on the rise?

Back 107

Facial spasms, ocular strabismus, muscle spasticity, muscle pain disorders (OL), headaches (OL), Excessive sweating, BPH (OL)

Front 108

Which drugs are selective Ganglionic Nicotinic receptor inhibitors? What responses do they elicit and when are they used?

Back 108

Mecamylamine and Trimethaphan are selective for both Symp. and Paras. ganglia. They block all reflex regulation of heart and BP and produce a complete loss of predominant tone. They are used during a hypertensive crisis or an aortic aneurism.

Front 109

Does Norepinephrine have greater Alpha effects or greater Beta effects? Which receptor subtype does it have the least affinity for?

Back 109

Alpha effects; Beta 2

Front 110

What two sympathetic receptors work together to raise blood pressure and how do they do it?

Back 110

Alpha1 (increased peripheral resistance) and Beta 1 (increased chronotropic/ionotropic efffect)

Front 111

When sympathetic tone on the heart is induced what is the reflex pathway that normally occurs and which adrenergic receptors are involved where?

Back 111

Alpha‐1 stimulation results in an
extreme elevation of peripheral resistance thus increasing blood pressure. This markedly increased
blood pressure leads to baroreceptor feedback that inhibits the beta‐1 stimulation. Thus what the patient is left with is an increased blood pressure as a result of increased peripheral vascular
resistance.

Front 112

When blood pressure is high because there is increased sympathetic tone leading to increased vascular resistance, is there high or low perfusion to the organs?

Back 112

There is low perfusion, even though BP numbers may appear normal, there is less blood flowing to where it needs to

Front 113

Epinephrine is a non-selective adrenergic agonist, but at low doses which type of receptors, Alpha or Beta, does it have the greatest affinity for?

Back 113

Beta

Front 114

With larger doses of Epinephrine which receptors, Alpha or Beta, are seen to have greater activity?

Back 114

Alpha. Thus, with higher doses of epinephrine you can induce norepinephrine-like symptoms.

Front 115

What are the most common indications for epinephrine?

Back 115

Cardiac arrest and Anaphylaxis

Front 116

Are dopamine's effects on the body constant or do they change with the dose given?

Back 116

Dopamine's effects are dose dependent

Front 117

Which receptors are preferentially stimulated and what response is seen when Dopmine is given in a low dose?

Back 117

Dopamine receptors; Dopaminergic effect (improving renal and mesenteric function)

Front 118

Which receptors are preferentially stimulated and what response is seen when Dopmine is given in a medium range dose?

Back 118

Beta receptors; Beta effects (chronotropic and inotropic effects on the
heart)

Front 119

Which receptors are preferentially stimulated and what response is seen when Dopmine is given in a large dose?

Back 119

Alpha receptors; Alpha effects (aka, norepinephrine effects on vasculature, “leave em
dead.”

Front 120

When is Dopamine indicated?

Back 120

In cardiogenic or septic shock

Front 121

Which type of adrenergic receptors does Isoproterenol work on?

Back 121

Beta; it is a non-selective beta agonist and has no effect on alpha receptors

Front 122

What kind of effect does Isoproterenol have on BP?

Back 122

It decreases Diastolic BP due to Beta 2 effects.

Front 123

When is Isoproterenol indicated?

Back 123

It is useful in the management of bradycardia, non severe
heart block or cardiogenic shock, until a more definitive treatment can be initiated (such as
transcutaneous pacing)

Front 124

How is Isoproterenol degraded?

Back 124

Isoproterenol is degraded by COMT

Front 125

What intracellular enzyme exists in the presynaptic terminals associated with mitochondria degrades norepinephrine?

Back 125

Monoamine oxidase (MAO); Catecholamine O-methyl Transferase (COMT)

Front 126

How much higher is [Ca++] in the extracellular fluid than in the cell?

Back 126

1000X higher extracellular

Front 127

What organ and tissue is parasympathetic innervation particularly important for? What molecular intermediate does it work through?

Back 127

It is important in the corpra of the penis for production of an erection. It works through increasing the production of NOS and NO, which vasodilates and allows more blood flow

Front 128

What are the mechanisms of action of Cocaine?

Back 128

Blocks the reuptake of norepinephrinefrom synaptic cleft, and impairs conduction of SA rhythm in the heart...increased action of norepi and impaired cardiac rhythm can lead to VFib in some people

Front 129

How do direct acting agonists of the sympathetic system work? What are they?

Back 129

They directly stimulate adrenergic receptors; they are Norepinephrine, Epinenphrine, and Phenylephrine

Front 130

How do indirect acting agonists of the sympathetic system work? What are they?

Back 130

They stimulate norepinephrine to be released from axon terminals and work on adrenergic receptors; they are Tyramine, Ephedrine, (dex)Amphetamine

Front 131

What is the rate limiting step in the biosynthesis of Norepinephrine and Epinephrine? Molecule negatively regulates this step?

Back 131

The cytosolic conversion of Tyrosine to Dopa via tyrosnine hydoxylase; Norepinephrine negatively regulates this step.

Front 132

What is the name of the condition associated with a secondary form of hypertension that is caused by a catecholamine secreting tumor originating most commonly in the spinal column? How do we limit catecholamine synthesis in these patients?

Back 132

Pheochromocytoma; we treat this by inhibiting the rate limiting step of Tyrosine conversion to Dopa and the progressive synthesis of catecholamines.

Front 133

Dopamine is converted to Norepinephrine what compartment of the neuron? how does it get there? and by what enzyme is it converted?

Back 133

In the NT vesicle; got there by VMAT in exchange for H+ ions; by dopamine beta-hydroxylase

Front 134

What is VMAT, its action, and which drug blocks its action?

Back 134

VMAT is the Vesicle MonoAmine Transporter, which imports dopamine into presynaptic vesicles in exchange for H+ ions for conversion into norepinephrine; Recerptine blocks the action of this transporter

Front 135

What is the main adverse side effect of Reserprine and why does it cause it?

Back 135

The main adverse side effect oof Reserprine is depression; Resprine causes depression because it inhibits VMAT in the CNS neurons and subsequent dopamine ---> norepinephrine conversion just like it does in the sympathetic neurons leading to the alpha receptors of the vascular smooth muscle

Front 136

MAO and COMT are both catecholamine degrading enzymes. Where is each found with respect to intra/extracellular compartments?

Back 136

MAO is found intracellularly, bound to the mitochondrial membrane. COMT is found in the extracellular space in the synaptic cleft

Front 137

What are two enzymes found in the terminals of sympathetic nerves are targeted to knock down the production of norepinephrine?

Back 137

Tyrosine hydroxlase (Tyrosine --> Dopa) and VMAT (Vesicle MonoAmine Transporter)

Front 138

If Alpha receptors are close to the nerve terminal which subtype are they? If they are far away which subtype are they?

Back 138

If they are close to the nerve terminal they are Alpha 1, if they are far away they are Alpha 2

Front 139

How do Alpha receptors exert their action in smooth muscle cells?

Back 139

They increase the cytoplasmic levels of Ca++ by releasing it from intracellular stores and increasing permeability from the extracellular compartment

Front 140

Why are Calcium channel blocking drugs such important antihypertensive drugs?

Back 140

Because they affect the sympathetic tone on blood vessels so effectively (and they affect ionotropic effects in the heart?)

Front 141

What four classes of drugs make up ~90% of the prescribed medications for patients that suffer from hypertension? What four mechanisms to they promote?

Back 141

Beta blockers (Decreased cardiac output), Ca++ Channel blockers (decreased sympathetic vasomotor tone), ACE inhibitors (decrease vasconstriction with ANGII, the most powerful constrictor known), Thiazide diuretics (decrease blood volume)

Front 142

Which enzyme does Cocaine Block at nerve terminals?

Back 142

NET- norepinephrine enzyme transporter; this block reuptake of norepi

Front 143

How do the indirect acting agents, Ephedrine and Amphetamine work at the nerve terminal?

Back 143

NET(Norepinephrine Enzyme Transporter) takes up the indirect acting agent and Norepinephrine is displaced from the cytosol in to the synaptic cleft where is can elicit its response

Front 144

How does Cocaine effect the action of indirect acting agents on the sympathetic system? (increase, decrease, no change?)

Back 144

Cocaine DECREASES the action of indirect acting agents because cocaine targets NET and this is the same transporter that takes up the indirect acting agents

Front 145

What purpose does the autoreceptor on the nerve terminal of sympathetic nerves serve, what type of receptor is it and what NT does it bind?

Back 145

The purpose is to attenuate the release of Norepinephrine; the receptor is and Alpha 2 receptor

Front 146

How can blocking some subtypes of Alpha receptors lead to an exaggerated response of Norepinephrine release?

Back 146

This is because there are Alpha 2 receptors on the presynaptic terminals that are involved in a negative feedback loop, that decrease the release of norepinephrine. When they are blocked, so is this feedback

Front 147

By definition, which receptors are located at the posynaptic end of the nerve terminal close to where the sympathetic nerves terminate 1) at vascular smooth muscle and 2) at the heart

Back 147

by definition 1) Alpha 1 and 2) Beta 2

Front 148

How does feedback on the presynaptic Alpha 2 autoreceptor decrease the release of Norepinephrine?

Back 148

By decreasing the ability of Ca++ to influx across the cell membrane during stimulation and thus inhibiting the exocytotic process and vesicle release of NE

Front 149

What is the mechanism of action that Calcium elicits to increase smooth muscle contraction?

Back 149

Ca++ bind with Calmodulin and phosphoylates myosin light chains to produce smooth muscle contraction

Front 150

How do Alpha receptors lead to the increase of Ca++ intracellularly?

Back 150

Stimulation of Phosphlipase C ---> IP3 ----> releases intracellular Ca++ stores and activates PKC at the membrane along with Ca++

Front 151

When we are stimulating Alpha 2 presynaptic receptors pharmacologically to suppress sympathetic tone, where is the anatomically site of action?

Back 151

The Nucleus Tractus Solitarius in the brain stem

Front 152

What change in the Frank-Starling curve indicates a positive ionotropic response?

Back 152

A shift in the curve up and left indicates a positive ionotropic response

Front 153

What change in the Frank-Starling curve indicates a negative ionotropic response?

Back 153

A shift in the curve down and to the right indicates a negative ionotrpoic response

Front 154

What causes positive ionotropic effects in the heart?

Back 154

Sympathetic stimulation, Beta 1 agonists, Digoxin

Front 155

What causes negative ionotropic effects in the heart?

Back 155

Heart Failure; or excess Beta Blockers

Front 156

How do Beta 2 receptors stimulate vasodilation?

Back 156

They stimulate the production of cAMP which acts to phosphorylate proteins in the membrane of the sarcoplamic reticulum. These phosyphorylated proteins take up the calcium from the cytosol and lead to decreased contraction and increased dilation

Front 157

What are the effects seen from stimulation of A1 postsynaptic adrenergic receptors?

Back 157

Vasoconstriction, mydriasis, contractions of GI and bladder SPHINCTERS

Front 158

What are the effects seen from stimulation of A2 postsynaptic adrenergic receptors?

Back 158

Vasoconstiriction (blood vessels)

Front 159

What are the effects seen from stimulation of A2 presynaptic adrenergic receptors?

Back 159

Decreases central sympathetic activity and inhibits the release of norepinephrine from sympathetic nerves (NTS & nerve terminals)

Front 160

What are the effects seen from stimulation of B1 postsynaptic adrenergic receptors?

Back 160

(+) Ionotropic and (+) chronotropic effects in the heart; there are also arrhythmogenic effects that can be observed especially when stimulated with high doses of agonist (these can be good if there is a heart block and no conduction, but usually bad and produce ectopic conduction)

Front 161

What are the effects seen from stimulation of B2 postsynaptic adrenergic receptors?

Back 161

Vasodilation, bronchodilation, mobilization of glucose and possibly fat stores (mechanisms mediated through cAMP)

Front 162

What are the effects seen from stimulation of B3 adrenergic receptors?

Back 162

Mobilization of fatty acids and breakdown of fat cells and adipose tissue

Front 163

What is the effect produced by Phenylephrine, which receptors does it stimulate and when is it indicated?

Back 163

Phenylephrine produces a long acting and long lasting rise in BP due to action on A1 receptors; this is indicated during spinal and general anesthesia, vascular shock, drug induced hypotension, overcoming paroxysmal supraventricular tachycardia

Front 164

Which receptors does Norepinephrine (Levophed) work on and why can't it be used in an acute asthmatic attack?

Back 164

It stimulates A1, A2, B1 >> B2; its effects on B2 are so minimal that it is not effective in an acute asthmatic attack

Front 165

Why do you get a smaller increase in BP when you use Epinephrine vs. Norepinephrine?

Back 165

This is because Epinephrine simulates B2 very well in addition to stimulating A1, A2, and B1 like NE. The vascular beds in Skeletal muscles are big and laden with B2 receptors, so when they dilate they can have a profound effect on BP. This attenuates the response of BP to Epi compared to the response of BP to norepi.

Front 166

Explain what type of shock is Isoproterenol good for treating and which type is it not? Why and how does it have to do with the receptors it stimulates?

Back 166

Isoproterenol stimulates B1 and B2 receptors only. Thus it is, Good for Cardiogenic shock where there is low cardiac output and increased output is needed. It is bad for anaphylactic shock or Gram (-) septic shock that are more due to vasodilation. Because of its powerful effects on the B2 receptors in the vascular beds of skeletal muscle it could exacerbate the problem

Front 167

What is stimulation of D1 dopamine receptors used for?

Back 167

To produce vasodilation of mesenteric and renal vessels to promote prefusion of mesentery and kidneys;

Front 168

What two types of receptors does Dopamine affect at higher concentrations?

Back 168

B1s and A2s, thus it helps support BP during shock and is used in acute heart failure

Front 169

What adrenergic agent stimulates only B1 receptors and is used in cardiogenic shock and heart failure?

Back 169

Dobutamine

Front 170

What is the major form of metabolism of Norepinephrine from the synaptic cleft?!?

Back 170

REUPTAKE!!!!

Front 171

What is the major metabolite of Norepinephrine and epinephrine that is produced in the liver (via MAO) from excess metanephrine and normetanephrine (metabolites that when epi and norepi are increased are found in the urine)? What condition would you expect to find in this patient?

Back 171

VMA; tremendously increased in pheochromocytoma tumor

Front 172

Where do we find Catechol-O-methyltransferase (COMT) in cells?

Back 172

Extracellularly, associated with membranes

Front 173

What intracellular enzyme degrades Tyramine?

Back 173

MAO

Front 174

What happens to the response elicited by Tyramine when Phenelzine (an MAO inhibitor) is given?

Back 174

It goes way up! Because MAO degrades neither Tyramine nor NE now!

Front 175

What foods contain Tyramine?

Back 175

Red wine, aged cheeses, smoked oysters

Front 176

What are MAO inhibitors traditionally used for?

Back 176

Depression

Front 177

What do patients taking MAO inhibitors have to be careful of concerning diet?

Back 177

They must not consume foods with large amounts of Tyramine in them! (or take ephedrine)

Front 178

What is the mechanism by which MAO inhibitors can help lower BP?

Back 178

By producing the false NT Octopamine. When low amounts of Tyramine in the diet are taken up by VMAT on the membranes of vesicles in nerve terminals, this Tyramine gets converted to Octopamine (an NT much weaker than NE, and an A2 blocker) by DBH. Octopamine helps lower blood pressure

Front 179

Do MAOIs have a bigger effect on NE or indirect acting adrenergic agents?

Back 179

Indirect acting!; no change is observed with the direct acting agents

Front 180

How much of the total NE pool in the vesicles of nerve terminals is released as a result of indrect sympathetic agonist action?

Back 180

about 3%

Front 181

Amphetamine, Ephedrine, Tyramine:
Of these drugs which are direct acting, indirect or both? If there is a direct effect, which adrenergic receptors are stimulated?

Back 181

Amphetamine- both indirect and direct action; simulates Alpha receptors
Ephedrine- both indirect and direct action; stimulates both Alpha and Beta receptors
Tyramine- indirect action only

Front 182

What is Tachyphylaxis?

Back 182

Tachyphylaxis refers to decreased response to the action of indirect acting adrenergic agonist upon successive dosing due to exhaustion of cytosolic NE

Front 183

What is the other drug that begins with an "I" that works on sympathetic nerve terminals through the same mechanism of action as Cocaine?

Back 183

Imipramine

Front 184

What effect does Reserpine pretreatment have on the action of indirect acting adrenergic agonists? WHY?

Back 184

It blocks the effects of indiirect acting adrenergic agonists because those drugs work through kicking out NE that is stored in the presynaptic vesicles. Reserpine blocks VMAT, the transporter that brings Dopamine into those vesicles, in order to make NE

Front 185

How does Bertylium exert its action at the end of sympathetic nerve terminals?

Back 185

It uncouples the release of vesicular NE from the action potential (Ca++ mediated event). Also used as a K+ channel blocker.

Front 186

What four other drugs does Guanethidine share mechanisms of action with?

Back 186

Tyramine (kicks out NE after being taken up by NET)

Cocaine (blocks NET reuptake of NE)

Reserpine (blocks VMAT and vesicular NE production)

Bertylium (dissociates vesicular release from action potential)

Front 187

What are the effects of Guanethidine on BP?

Back 187

Initially it acts like Tyramine and Cocaine and raises BP due to vasocontriction.

Later it acts like Reserpine and Bertylium and lowers BP due to vasodilation.

Front 188

Why can't we give ACE inhibitors to women?

Back 188

Because ANGII is a growth factor, so anything that would inhibit its effects iis absolutely contraindicated in pregnant women

Front 189

What is a substitute medication that we give to pregnant women in place of an ACE inhibitor? How does it work?

Back 189

Alpha-methyldopa; it works much like the MAOI + Tyramine mechanism ---> it produces alpha-methylnorepinephrine in vesicles, which acts as a false NT and stimulator of presynaptic A2 receptors at the nerve terminals and NTS (negative feedback on NE release)

Front 190

Which receptors do each of these drugs work on?
1) Dobutamine
2) Albuterol
3) Terbutyline
4) Phenylephrine
5) Clonidine
6) Dopamine

Back 190

1) B1
2) B2
3) B2
4) A1
5) A2
6) D1>>B1 and A2

Front 191

What do you give a patient with Gram (-) sepsis?

Back 191

Dopamine; but if you have to continually increase the concentration to try and produce effects there is risk of extreme vasoconstriction and arrhythmias

Front 192

What percentage of the heart's fuel comes from free fatty acids?

Back 192

~70%

Front 193

What drug is the most potent effector of B1 and B2 receptors because of it's two methyl groups the end of the molecule?

Back 193

Isoproterenol

Front 194

What is tocolytic action (B2 manipulation)?

Back 194

Tocolytic action means relaxation of the Urterus- can stop contraction if necessary, such as in the case of early labor

Front 195

What type of signal transducing proteins do Beta and Alpha receptrors work through? Which subtype specifically for Betas regardless of whether they contract or relax? Which for postsynaptic A2s?

Back 195

They both work through G protein signaling mechanisms. Betas work through Gs proteins and postsynaptic A2s work through Gi proteins (but, still have net increase on cytoplasmic Ca++)

Front 196

How do B2 receptors work to produce a smooth muscle relaxation? What is the key ion in the cell and does its cytoplasmic level increase or decrease?

Back 196

B2 works by decreasing the cytosolic levels of Ca++, and facilitating its uptake into intracellular stores. Increased levels of cAMP activate cAMP dependent kinase phosphorylates special proteins on the SR and Ca++ is taken up into store

Front 197

How do B1 receptors work to produce increased contractility? What is the key ion in the cell and does its cytoplasmic level increase or decrease?

Back 197

B1 works by increasing the cytosolic levels of Ca++, and facilitating its release from intracellular stores. Increased levels of cAMP activate cAMP dependent kinase phosphorylates special proteins on the SR and Ca++ is released from store. There is also more Ca++ that enters from the extracellular compartment through the L-type channel

Front 198

How do postsynaptic A2 receptors work to produce smooth muscle contraction? What is the key ion in the cell and does its cytoplasmic level increase or decrease?

Back 198

Postsynaptic A2 receptors stimulat Gi protein activity and decrease levels of intracellular cAMP. Still, there ends up being net increase in cytosolic levels of Ca++ and thus increased contraction of smooth muscle.

Front 199

Which medications are non-selective Alpha receptor agonists only?

Back 199

None

Front 200

Which medications are non-selective Beta receptor agonists only?

Back 200

Isoproterenol

Front 201

Which medications are non-selective Beta and Alpha receptor agonists only?

Back 201

Epinephrine

Front 202

Which medications are non-selective Alpha receptor agonists and Selective Beta receptor agonists only?

Back 202

Norepinephrine; only B1

Front 203

Which medications are selective Beta1 receptor agonists only?

Back 203

Dobutamin

Front 204

Which medications are selective Beta 2 receptor agonists only?

Back 204

Tertbutyline and Albuterol

Front 205

Which medications are selective Alpha 1 receptor agonists only?

Back 205

Phenylephrine and Methoxamine (rebound vasodilation can be a problem)

Front 206

Which medications are selective Alpha 2 receptor agonists only?

Back 206

Clonidine and Methyldopa (can use in preeclampsia- Hypertension during preganancy)

Front 207

What alpha 1 stimulator is commonly used as a nasal decongestant?

Back 207

Phenylephrine

Front 208

Which adrenergic stimulators are considered Catechols?

Back 208

Catechol, Phenylethylamine, Norepinephrine, Epinephrine, Isoproterenol, Dopamine

Front 209

Which adrenergic stimulators are not considered Catechols?

Back 209

Phenylephrine, Methoxamine, Ephedrine, Amphetamine

Front 210

What drug would you use to test whether or not the effect of an adrenergic stimulator was direct or indirect?

Back 210

Cocaine, because it definitively only blocker the action of an indirect stimulator

Front 211

What are the major uses for Beta Blocking drugs?

Back 211

Hypertension, Ischemic Heart Disease/Angina, CHF,

Front 212

Which drugs are Non-selective Alpha blocking agents?

Back 212

Phentolamine and Phenoxybenzamine

Front 213

Which drug is a Non-selective Beta blocking agent?

Back 213

Propranolol

Front 214

Which drug is a selective A1 blocking agent?

Back 214

Prazosin

Front 215

Which drug is a selective B1 blocking agent? What is it used for?

Back 215

Metoprolol; antianginal, antihypertensive, asthmatic patients with caution, Hypertensive with CHF, CHF

Front 216

Which drug is a selective A2 blocking agent?

Back 216

Yohimbine

Front 217

Which drug is a selective B2 blocking agent?

Back 217

Butoxamine

Front 218

Do the Non-specific Alpha blocking agents have much use in medicine today? Why or why not? Which is competitive and which is non-competitive? What special case could they be used for?

Back 218

They do not have much use today, mostly because they have not proven to be that effective at reducing hypertension and they have undesirable side effects (Reflex tachycardia). Phenoxybenzamine (long-acting)is a non-competitive inhibitor and Phentolamine (short-acting) is a competitive inhibitor. They could be used in the special case of Pheochromocytoma.

Front 219

What are two main uses that A1 blockers are used for? What is the main example of this class?

Back 219

Hypertension and Benign Prostatic Hyperplasia (BPH); the main example is Prazosin

Front 220

What purpose do A2 receptor blockers serve?

Back 220

They block the A2 receptors in the NTS so they there is less feedback inhibition of Norepinephrine and you get a better reflex response when the sympathetic system is stimulated say in the case of blood flow and a change in posture

Front 221

What are the three drugs we can use to treat Glaucoma and which classes do they belong to?

Back 221

Pilocarpine (Cholinomimetic), Echothiophate (AchEI), Propranolol (Beta-blockers)

Front 222

Why do Non-selective Alpha blockers give reflex tachycardia and the Selective A1 blockers do not?

Back 222

Because with the Non-selective Alpha blockers the negative feedback on Norepinephrine of the presynaptic A2 receptors in the Sinus Node is not in tact, whereas with the selective A1 blockers it is.

Front 223

What is Dyslipidemia?

Back 223

This is a general term associated with high cholesterol or high triglyceride levels in plasma

Front 224

What are the two major sequelae of hyperlipidemia?

Back 224

Acute pancreatitis and atherosclerosis

Front 225

Explain what each of the three carrier molecules are used for: Chylomicrons, vLDL, LDL.

Back 225

Chylomicrons are formed in the intestines and are for transporting TGs of dietary origin to the liver. vLDL is secreted by the liver and provides a means for TG from the liver to be exported to the tissues. LDL transports cholesterol from the liver to the blood stream, and high levels of this are associated with increased risk of atherosclerosis and Coronary Artery Disease

Front 226

Where does HDL transport cholesterol to and from?

Back 226

HDL transports cholesterol from the periphery back to the liver

Front 227

Describe Familial Hypercholesterolemia and what its underlying mechanism is. How would you treat it?

Back 227

Familial Hypercholesterolemia is an autosomal dominant trait which produces a defect in the affinity of LDL receptor. Homozygous individuals can have serum cholesterol levels as high as 1000mg/dl (This would lead to childhood development of coronary disease). Niacin and Atorvastatin are beneficial, but binding resins have little to no effect depending on LDL receptor activity.

Front 228

Describe Familial Ligand-Defective Apolipoprotein B Dyslipidemia.

Back 228

This comes from a defect in ligand region of apo B100 region of LDL; impairs the endocytosis of LDL leading to moderately severe hypercholesterolemias

Front 229

How do we treat Familial Ligand-Defective Apolipoprotein B Dyslipidemia.

Back 229

Statins (upregulators of LDL receptors) have variable effects; Niacin produces beneficial effects by reducing vLDL plasma levels

Front 230

What enzyme determines the rate of Triglyceride clearance?

Back 230

Lipoprotein lipase.

Front 231

What 4 conditions are associated with secondary dyslipidemias?

Back 231

Diabetes(both high TG and cholesterol), Hypothyroidism(high cholesterol, but normal TG), BC Pills(high cholesterol and TG), Drug Induced Dyslipidemia

Front 232

How does Niacin work to improve a person's lipid profile?

Back 232

It decreases LDL and vLDL levels, and raises HDL levels; the mechanism involves the inhibition of vLDL secretion there by reducing LDL levels. Also lowers both TG and Lp(a) levels

Front 233

What are some of the side effects of Niacin? Drug interactions?

Back 233

Niacin flushing, hyperuricemia, hepatic dysfunction; works synergistically with ganglionic blockers leading to orthostatic hypotension

Front 234

Name two medications that are Fibric Acid derivatives?

Back 234

Gemfibrozil and Fenofibrate

Front 235

What is the mechanism of action of Gemfibrozil and Fenofibrate? What conditions are they used to treat?

Back 235

They reduce vLDL levels and increase the activity of lipoprotein lipase, and also lower TGs and raise HDL. These medications are used to treat Hypertriglyceridemias in which vLDLs predominate and dysbetalipoproteinemia

Front 236

What are some of the side effects of Fibric Acid derivatives?

Back 236

Myopathy, arrhythmias, elevation of liver enzymes, cholesterol gallstones, increased anticoagulant effect of coumarin and indandeiones.

Front 237

What medications are members of the class Bile Acid Binding Resins?

Back 237

Colestipol and Cholestyramine

Front 238

How do Colestipol and Cholestyramine work?

Back 238

These medications bind bile acids in the intestine forming a complex that is excreted in the feces. This prevents the reabsorbtion and recycling of bile acids and so the body increases the oxidation of cholesterol to bile acids to replenish what was lost. This decrease in cholesterol results in an increase in the number of LDL receptors, which thereby decrease the serum LDL levels

Front 239

What are some of the side effects of the bile acid binding resins?

Back 239

constipation, may interfere with normal fat digestion and absorption, may prevent the absorption of fat soluble vitamins such as A, D, E, and K

Front 240

What do statins do? How do they work?

Back 240

Statins are structural analogs of HMG-CoA and are competitive inhibitors of HMG-CoA reductase; this is the enzyme that mediates the first committed step in sterol biosynthesis; This leads to an induction of High Affinity LDL receptors, thus a lowering of serum LDL levels (may also have an effect on C-reactive protein)

Front 241

Why are Statin drugs usually taken at night? Which Statin is an exception and why?

Back 241

This is because cholesterol metabolism usually occurs, and is at its highest, at night time. The drug is not taken to maintain constant levels because tolerance is a concern. The exception to this is the drug Atorvastatin. This can be taken at other times because it has such a long half life that plenty of drug is left around at night

Front 242

Which Statins are special in that the are pro-drugs and must be activated in the intestine vs. the rest of the Statins, which are ingested in active forms?

Back 242

Lovastatin (Mevacor) and Simvastatin (Zocor) are inactive prodrugs that are activated in the GI tract

Front 243

Which Statin is nearly completely absorbed?

Back 243

Fluvastatin (Lescol)

Front 244

What metabolic liver effect is observed to be high in Statins?

Back 244

There is a high first pass liver effect

Front 245

What is the average half life associated with most Statin drugs? Which is the exception and what is its half life?

Back 245

The average half life of a Statin is 1 to 3 hours; the exception to this is Atorvastatin (Lipitor) which has a half life of about 14 hours

Front 246

What are some common side effects of taking Statins? What is a less common effect that is more serious?

Back 246

It is common to see 3x elevation of liver enzymes in the serum, which does not need to alarm for liver toxicity unless there is already underlying liver disease in the patient. A less common side effect is RHABDOMYOLYSIS which may occur leading to myoglobinemia and subsequent RENAL FAILURE

Front 247

Drugs interaction that effect what molecules in the liver must be considered when prescribing Statins?

Back 247

Those drugs that affect Cytochrome metabolism; drugs that inhibit or compete for CYP3A4 or CYP2C9 will increase Statin levels in plasma; drugs that induce CYP450s will reduces Stain levels in plasma

Front 248

Can we give Statins to pregnant women?

Back 248

NO! they have TERATOGENIC potential!!!

Front 249

How does Ezetimibe work? Is it a prodrug or already active?

Back 249

This is a prodrug that works by decreasing GI uptake of cholesterol (both dietary and biliary secreted cholesterol). This reduces the tightly regulated cholesterol pool in the liver resulting in invreased synthesis of high affinity LDL receptors and subsequent removal of LDL from the blood. This lowers serum LDL and TGs!!

Front 250

What is the toxicity associated with Ezetimibe and HMG-CoA reductase inhibitors (Statins)?

Back 250

They may increase hepatic toxicity when administered together.

Front 251

Why is it standard therapy to initiate HMG-CoA Reductase Inhibitor Therapy immediately after myocardial infarction, irrespective of lipid levels?

Back 251

This is because in addition to inhibiting cholesterol synthesis, these drugs decrease oxidative stress, as well as vascular inflammation and promote increased stability of atherosclerotic lesions.

Front 252

What are the effects of Fibric acid derivatives on the lypolysis of lipoprotein TGs and in adipose tissue? What receptors do they bind to?

Back 252

Lipoprotein TG lypolysis is increased, while intracellular lipolysis in adipose tissue is decreased. Fibric acid derivatives function as ligands for the nuclear transcription receptor "peroxisome proliferator-activated receptor alpha (PPAR-alpha)"

Front 253

What are the lipid molecules and receptors that each of these drug classes works to reduce or increase:
1) Bile acid binding resins
2) Niacin (Nicotinc acid)
3) Fibric acid derivatives
4) Statins

Back 253

1) Isolated decrease in LDL and IDL; increases LDL receptor
2) Decreases in vLDL, LDL, and TGs; increases HDL (most effective agent at doing this)
3) Decreases vLDL, LDL, and TGs; slight HDL increase
4) Decreases vLDL and LDL; increases LDL receptors

Front 254

Explain Variant Angina? What is another name for this condition?

Back 254

Variant angina is a coronary insufficiency syndrome due to VASOSPASM (can appear in the absence of CAD). This may be an effect due produced by atherosclerosis on vasomotor tone. Attacks often occur during rest (e.g. at night). It is also called PRINZMETAL'S ANGINA.

Front 255

What is the pain and ischemia associated with Unstable Angina due to?

Back 255

Platelet aggreagation at fractured plaques and some vasospasm

Front 256

What are the main therapeutic features of Nitrates, Calcium Channel blockers and Beta Blockers?

Back 256

Nitrates are vasodilators with a large preference for veins; Calcium Channel blockers are vasodilatory and cardiac depressants; Beta blockers serve as cardiac and sympathetic tone depressents

Front 257

Why do organic nitrates (e.g. Nitroglycerin) work through vasodilation preferably of the Veins? What is the theory behind the mechanical heart change of why Nitros work? What is a counter-productive side effect that they can elicit?

Back 257

Nitroproduces a greater effect on the veins than the arteries because there is more enzyme that converts nitroglycerin to NO in venous smooth muscle vs. atertial. Venodilation results in decreased preload, which leads to decreased work. Decreased work leads to decreased O2 demand less ischemia; Reduction of afterload which can be produced by high doses and arterial dilation can elicit a counter productive reflex tachycardia

Front 258

Explain the molecular mechanism and pathway that accounts for the action of Organic nitrogen administration.

Back 258

Nitroglycerine is converted to and stimulates NO production in endothelial cells. NO acts stimulates Guanylyl cyclase which converts GTP to cGMP. cGMP facilitates dephosphorylation of Myosin-LC (no longer interacts well with actin) and protein kinase mediated intracellular Calcium decrease

Front 259

What are two effects that Nitrates have on the coronary circulation?

Back 259

1) They redistribute coronary blood flow and can selectively increase blood flow to ischemic areas, with overall blood flow not being increased.
2) There is a reversal of coronary vasospasm

Front 260

What strategy is employed with patients taking nitrates, to avoid tolerance?

Back 260

Nightly nitrate free gaps; not taking nitrates at night

Front 261

Describe some of the side effects and drug interactions seen with Nitrates.

Back 261

Side effects: Orthostatic hypotension, headache, dizziness, reflex tachycardia, tolerance

Interactions: when taken within 24 hrs of Sildenafil (Viagra) can produce >25mmHg drop in blood pressure

Front 262

What is a mechanism of action associated with Beta blockers (Propranolol) with regard to oxygen consumption?

Back 262

They reduce heart rate and force of contraction of the heart, as well as reduce blood pressure during exercise. All this decreases the work of the heart and the O2 demand.

Front 263

What type of angina are Beta blockers (Propranolol) indicated for? What type are they contraindicated for?

Back 263

They are used for prophylaxis of exertional angina only (keeps systolic BP and HR low = low O2 demand); They are contraindicated for Variant Angina which is more due to vasospasm (Beta blockers could exacerbated the problem)

Front 264

Why are Beta blockers frequently administered with Nitrates?

Back 264

Because a side effect of Beta blockers is increased end-diastolic volume and ejection time (increases O2 demand), Nitrates are often coadministered to decrease this end-diastolic volume and preload

Front 265

What is the gold standard of treatment for OD of Beta blockers and toxic exposure on heart rate? How does this treatment work?

Back 265

Glucagon; it works because it has receptors in the heart like Beta receptors that work through a similar pathway and has similar effects as the Beta receptors

Front 266

Describe the channels that Calcium Channel blockers act on in cardiac and vascular smooth muscle in order to produce their effect of decreased contractilty and vasodilation.

Back 266

The drugs block calcium influx via L-type channels in cardiac and vascular smooth muscle

Front 267

Which Calcium Channel blocker is "vascular selective"? What are one of the problems associated with these vascular selective dihydropyridines?

Back 267

Nifedipine (Procardia); one of the problems with these types of Ca++ blockers is reflex tachycardia

Front 268

What are the three main Ca++ channel blockers that we learned about? When are they commonly used and when are they contraindicated?

Back 268

Nifedipine, Diltiazem, Verapamil; they are commonl used as antiarrhythmic agents, they are options to Beta Blockers in asthmatics and useful if patients have A.Fib; they are contraindicated in decreased AV conduction (CHF, AV-block), avoid combining with Beta blocker (decreased HR/decreased SV)

Front 269

What is the most important physical mechanism by which the Ca++ Channel Antagonists work (affects arteries more than veins)?

Back 269

Decrease O2 demand through decreased HR, Contract., TPR, BP and increase coronary blood flow (useful in vasospastic angina)

Front 270

What type of Ca++ blockers are less effective as a monotherapy and why?

Back 270

The Dihydropyridine type CCBs because they have vascular selective resistance

Front 271

Explain why the drug combination of Nitrates and Beta blockers is beneficial for patients with Angina?

Back 271

They work by different mechanisms of action so their effects are additive. Beta blockers prevent reflex tachycardia of nitrates and nitrates reduce increased end-diastolic volume from Beta blockers

Front 272

Explain what Ranolazine is used for and how it works.

Back 272

Ranolazine is an alternative antianginal drug for those who can't tolerate other antianginal's side effects. It works by shortening the action potential duration by blocking the surface membrane Na ion channels. This decreases intracellular Ca++ and O2 demand.***Higher doses increase QT by blocking the Potassium Kr channels

Front 273

What is Clopidogrel and how does it work?

Back 273

Clopidogrel is a pro-drug whose action may be related to adenosine diphosphate (ADP) receptor on platelet cell membranes. The specific subtype of ADP receptor that clopidogrel irreversibly inhibits is P2Y12 and is important in platelet aggregation and the cross-linking of platelets by fibrin. The blockade of this receptor inhibits platelet aggregation by blocking activation of the glycoprotein IIb/IIIa pathway.

Front 274

Which two hypolipidemic drug classes are not combined because of exacerbation of potentially harmful side effects?

Back 274

Statins and Fibrates